DEXFENFLURAMINE TREATMENT INFLUENCES PLASMA-CATECHOLAMINES AND ENERGYSUBSTRATE METABOLISM IN RATS

The effect of chronic intragastric administration of dexfenfluramine ( FFL, 1 mg/kg, twice a day), a drug that increases serotonergic transmi ssion, on peripheral energy substrate metabolism was investigated. Rat s were provided with permanent cannulas, allowing stress-free intragas tric treatment and blood sampling. Fenfluramine-treated and control an imals were submitted to strenuous swimming at days -2, 1, 4, and 7 rel ative to the onset of FFL treatment at day 0. Blood samples were taken before, during, and after exercise. Thereafter, possible changes in c atecholamine sensitivity were investigated during intravenous infusion s of norepinephrine (NE) and epinephrine. Finally, energy expenditure, including resting respiratory quotient (RQ), and carbohydrate and fat utilization were measured under baseline conditions. It was found tha t chronic administration of FFL led to a transient reduction in the ex ercise-induced increase of blood glucose concentrations. Plasma norepi nephrine responses to exercise gradually increased in the FFL-treated animals. Baseline RQ was markedly increased in the FFL-treated animals , indicating an increase of carbohydrate utilization and a decrease of fat combustion. Total energy expenditure remained unchanged. The incr eased RQ was accompanied by increased sensitivity for NE and significa ntly decreased baseline concentrations of plasma free fatty acids.